Veterinary delivery systems and methods of delivering effective agents to animals

ABSTRACT

A veterinary delivery system in the form of a pliable film comprising at least one binder, at least one lubricant, at least one solvent for the binder and lubricant, and an effective amount of at least one effective agent. According to one embodiment, a flavorant is included in a pliable hydrophilic film in order to enhance oral acceptability by the animal. In other embodiments, the films preferably have a moisture content of about 2-15%, preferably about 3-7% by weight. The hydrophilic films most preferably have at least one effective agent distributed homogeneously throughout the film.  
     Also disclosed are methods of delivering veterinary delivery systems wherein a pliable, hydrophilic film comprising at least one effective agent is placed within the oral cavity of an animal.

[0001] The present invention is directed to veterinary care and, moreparticularly, to veterinary delivery systems and methods of deliveringeffective agents to animals.

BACKGROUND

[0002] Effective veterinary care is very important to animal owners aswell as the rest of society. Many people own household pets, such asdogs and cats, and often become emotionally attached to those pets.Other animals, such as dogs used for police work and search and rescueoperations, race horses, etc, each play a significant role in society.The proper and efficient veterinary care of these and other animals isvery important.

[0003] The administration of pharmaceuticals, such as antibiotics,anti-inflammatory agents, anti-viral agents, vaccines and wormers, areimportant to the health of these animals. Typical methods ofadministering pharmaceuticals to animals include vascular injections,muscular injections and oral administration of liquids or pills.Disadvantages of these known pharmaceutical delivery methods includedifficulty in administration, pain to the animals, difficulty inmeasuring the dosages when liquids or pills are added to animal feed,since, for example, some time a number of animals will share a commonfeed container and animals will sometimes try to spit out medicine.

[0004] It would therefore be desirable to provide a delivery system foreffective agents which is easier to administer. It would also bedesirable to provide veterinary delivery systems which have a higherdose delivery accuracy than previous feed-mixed delivery systems.

[0005] It would also be desirable to provide a veterinary pharmaceuticaldelivery systems that can be at least partially absorbed into theanimals vascular system through mucous membranes while other portionsare ingested.

[0006] It would also be desirable to provide methods for deliveringagents, effective in the care of animals which provide quick efficacy,are easier to store, have longer storage shelf lives and which are lessprone to being spit out by the animal receiving the effective agent.

SUMMARY OF THE INVENTION

[0007] One aspect of the present invention comprises a veterinarydelivery system in the form of a pliable hydrophilic film comprising atleast one binder, at least one lubricant, at least one solvent for thebinder and lubricant, and an effective amount of at least one effectiveagent. As used herein, the term “effective agent” is meant to includeany compound which has an effect upon one or more health properties ofthe recipient animal. For example, effective agents include compoundswhich are therapeutically active and are designed to treat a symptom ofthe animal such as illness, bad breath, incontinence, or othersdiscussed below. An effective agent can also comprise a compound havingcosmetic effects which will change any visual aspect of the animal, suchas an agent which is designed to provide a healthier coat. Otherpharmaceuticals are also included such as pharmaceutical actives, and isnot limited to prescription medicines.

[0008] According to another preferred embodiment of the presentinvention, at least one flavorant is also included in a pliablehydrophilic film in order to enhance oral acceptability by the animal.

[0009] According to another aspect of the present invention, filmspreferably have a moisture content of not greater than about 15% byweight and most preferably have moisture content of about 37% by weight.The hydrophilic films most preferably have at least one effective agentdistributed homogeneously throughout the film.

[0010] The present invention also comprises methods of deliveringeffective agents wherein a tacky hydrophilic film comprising at leastone effective agent is placed within the oral cavity of an animal.

[0011] These and other embodiments of the present invention aredescribed in greater detail below.

DETAILED DESCRIPTION

[0012] The various aspects of the present invention relate to veterinarypharmaceutical delivery systems and methods of delivering effectiveagents to animals. As used herein, the term “animals” is meant toindicate mammals, and to exclude humans. The novel methods and deliverysystems described herein utilize a pliable, preferably hydrophilic, filmwhich contains an effective amount of at least one effective agent. Thepreferred films of the present invention advantageously becomesufficiently sticky upon contact with the mucousal membrane or tongue ofan animal such that the film adheres to the animal's tongue or mucousalmembrane and generally is difficult to spit out or be dislodged. Thefilms are sticky upon contact due to their hydrophilic nature andrelatively low initial moisture content. In order to further enhance theretention of the delivery systems films by the animal, preferredembodiments of the present invention also advantageously compriseflavorants which are particularly adapted to be acceptable by theparticular animal.

[0013] One embodiment of the present invention comprises a pliable filmcomprising at least one binding agent, at least one lubricant, a solventfor the binding agent and the lubricant, and an effective amount of atleast one effective agent. The binding agent provides the structuralintegrity to the pliable film, either chemically or physically, and maycomprise polyvinyl alcohol, methycelluloses such as hydroxypropylmethylcellulose (HPMC) or carboxymethylcellulose, gelatins, starches,either alone or in combination. The final film comprises up to about 95%by weight of the binding agent, and preferably about 40% to 90% byweight, more preferably about 50% to 75% by weight.

[0014] The lubricant can comprise one or more of glycerins, glycols suchas propylene glycols, oils such as fish oils or vegetable oils, andcombinations thereof. The lubricant of the final film should generallybe not greater than about 45% by weight of the final film, preferablynot greater than about 25%, more preferably about 2 to 15% and mostpreferably about 4 to 8% by weight. Unless otherwise stated in thisapplication, all percentages are by weight and are expressed as apercentage of the final film.

[0015] In order to properly blend the binding agent and lubricant, asolvent such as water or an organic solvent such as ethanol ispreferably employed. In the final film, the solvent preferably comprisesabout 2 to 15% by weight of solvent and most preferably about 3 to 7% byweight. If desired, more than one solvent can be used.

[0016] The effective agents of the present invention can comprise a widerange of therapeutic actives, cosmetic agents and other veterinarypharmaceuticals such an antibiotics, pain relievers, anti-inflammatoryagents, anti-viral agents, vaccines, wormers, heart wormers, nutritionalsupplements, hypothyroidism medication, arthritis medication,incontinence medication, agents for the control of tartar and plaque,pain relievers, agents for treatment of bacterial diseases andcoccidiosis, and combinations thereof. For example, the effective agentscan comprise antibiotics such as sulfamethoxazole combined withtrimethoprim (ditrim), penicillin, amoxicillin, ampicillin, cephalexin,metronidazole, hypothyroidism medication, such as levothyroxine, agentsfor treatment of bacterial diseases and coccidiosis such assulfadimethoxine, pain relievers such as buffered aspirin andprednisone, arthritis medication such as glucosamine HCl, chondroitinsulfate extracts (shark cartilage), minerals-calcium, manganese,magnesium, ascorbic acid (vitamin C), wormers and heartwormers such asivermectin, fenbendazole, milbemycin oxime, filaribits, parentalpamoate, toluene, dichlorophene, piperazine, and agents for the controlof tartar and plaque such as tetrasodium pryrophosphate. The amount ofthe active ingredient employed in the initial mixture will depend uponthe desired dosage. According to preferred embodiments of the presentinvention, the effective agent is preferably homogeneously distributedthroughout the film.

[0017] In order to enhance the acceptability of the delivery systems ofthe present invention, preferred embodiments comprise flavoring agentssuch as beef, chicken, liver, bacon, cheese, apple, smoke, fish, mintsuch as spearmint or peppermint, and combinations thereof and others.

[0018] Various embodiments of the present invention can also comprisefillers to modify the taste, texture, palpability, stickiness, aroma orroughage characteristics of the film. Fillers can be readily chosen andcan include fillers such as cornmeal, cornstarch, potato starch, bonemeal, corn syrup, wheat germ, brewers yeast, xanthan gum, carrageenanand combinations thereof.

[0019] It is also in the scope of the present invention to includepreservatives such as methyl paraben, propylparaben,ethylenediamine-tetraacetic acid (EDTA), stearic acid, diazolidinylurea, imdiazolidinyl urea, and combinations thereof in order to enhanceshelf stability and minimize microbial growth from contamination.

[0020] The delivery systems of the present invention can advantageouslybe manufactured on a bulk scale. In order to achieve the desiredconcentration of effective agent in the dosage form, preferredembodiments are manufactured on a weight by weight concentration of thetotal product. While the following description utilizes water-solubleingredients, based upon the solubility of the effective agent, the basecan be formulated to be either water soluble or non-water soluble.

Compounding:

[0021] Ingredients are individually weighed or otherwise measured. Someformulas require an emulsion to be formed, based on the solubility ofthe active or other ingredients. Some ingredients may need to becombined in a series of smaller tanks, prior to being added to a largertank, again depending on solubility, temperature and mixingcharacteristics. The ingredients are mixed and/or heated accordinglyuntil a homogeneous solution is achieved. Because certain ingredientswill require heat to aid dissolution, the tanks can be heated to reducemixing time and increase ingredient solubility. The bulk can be used hotor cooled based on viscosity and physical characteristics required forthe next phase of manufacturing.

Distribution and/or Transfer onto Belt:

[0022] The second step involves the transfer of the bulk evenly and atthe desired thickness onto a belt or sheet of material that will bepassed into an oven or otherwise treated to remove the majority of thesolvent, e.g. water, from the blend. The belt itself can be made of anumber of different materials including stainless steel, teflon,aluminum, a high temperature chemical resistant polymer, or metal alloyamong others. The belt's physical dimensions are based on the width ofthe bulk film roll desired, and the temperature of the oven. There are anumber of ways to cast or spread a bulk solution onto the belt evenlyand in a manner which advantageously free from bubbles and striations.The following are some of these methods. (1) The bulk can be pumped ontothe belt and spread with a blade or brush type device into an evendisplacement. (2) The bulk can be pumped through a slot dye, with acontrolled head pressure, e.g. from about 10-200 psi., onto the beltwith dimensions that provide an even displacement of liquid bulk. (3)The bulk can be sprayed through a series of nozzles onto the belt. (4)The bulk can be spread thinly and evenly by mechanical means. (5) Thebulk can be poured onto the belt and allowed to run or be blown byforced air to an even distribution. The conveyor type belt system is setto move the product at a controlled speed to achieve the desired dryingof the product. For example, the belt can advance the product from 2 to35 feet per minute depending on the moisture in the product, dryingrate, and the desired thickness. The films of the present inventiongenerally should have thicknesses not greater than about 0.05 inches,preferably not greater than about 0.025 inches, and most preferablyabout 0.0005 to about 0.010 of an inch.

Evaporation:

[0023] The belt passes through an oven or other type environmentalchamber at a controlled speed, humidity, ventilation, and temperature toeliminate enough of the solvent to produce a film of the desiredconsistency. To accomplish this, the belt speed and oven temperature iscontrolled to avoid any degradation of the components while eliminatingenough solvent from the formulation to achieve the desired pliability ofthe finished film. The optimal conditions are typically between about35° C. and 100° C. The result is sheets of film approximately the widthof the belt and the desired thickness. This bulk film contains a knownpercentage of active drug product.

[0024] The physical dimensions of the finished product typically canrange in size from about 10-80 millimeters square, depending on the sizeof the dose to be delivered. The films of the present invention can belarger, smaller or a different shape without departing from the scope ofthe present invention.

[0025] A person administering the dosage preferably places the film onor under the tongue, between the cheek or gum, or on the pallet of theanimal where the film will advantageously adhere and begin to dissolve.As the film dissolves, the effective agent is released and absorbedthrough the mucous membrane in the mouth and/or the gastro-intestinaltract.

[0026] Another aspect of the present invention is a method of deliveringan effective agent to an animal comprising the steps of a method ofdelivering an effective agent to an animal comprising the steps ofproviding a pliable film comprising at least one binder, at least onelubricant, at least one solvent for said binder and said lubricant, andan effective amount of at least one effective agent; and placing saidfilm within the oral cavity of said animal, e.g. manually. These filmsare preferably hydrophilic.

[0027] According to a still further embodiment, the film is placedwithin the oral cavity of an animal by first placing the film on aninsert device and then placing at least a portion of the insert devicewithin the oral cavity of the animal. The film can be adhered to thetongue of the animal or to a mucous membrane in the oral cavity.

[0028] Another aspect of the present invention comprises a method ofdelivering an effective agent utilizing a film, most preferably ahydrophilic film into the oral cavity of an animal. Those skilled in theart will appreciate that the veterinary care provider may not wish toinsert his hand into the oral cavity of certain animals. Therefore,according to another aspect of the present invention, a film of thepresent invention is placed on an insert device and a portion of thatinsert device is placed within the oral cavity of the animal. The insertdevice can comprise a wooden dowel, a plastic applicator, somethingedible, such as a carrot or other vegetable matter, a baked item such asa bread stick or pretzel, or can be forced via pressurized air through ahollow tube into the animal's oral cavity.

[0029] According to another embodiment of the present invention, aplurality of effective agents are provided within a single film. Forexample, according to one embodiment, one effective agent is preferablyabsorbed transbuccally at a faster rate than a second effective agentwhich is provided in that same film. For example, the second effectiveagent may have time-release properties which, when ingested, providesustained release over some period of time.

1. A veterinary delivery system comprising: a pliable film comprising atleast one binder, at least one lubricant, at least one solvent for saidbinder and said lubricant, and an effective amount of at least oneeffective agent.
 2. A veterinary delivery system according to claim 1wherein said effective agent is a pharmaceutically active component. 3.A veterinary delivery system according to claim 1 wherein said effectiveagent is a therapeutic agent.
 4. A veterinary delivery system accordingto claim 1 wherein said effective agent is a cosmetic agent.
 5. Aveterinary delivery system according to claim 1 wherein said filmfurther comprises a flavorant.
 6. A veterinary delivery system accordingto claim 2 wherein said flavorant is selected from the group consistingof genuine and artificial beef, chicken, liver, bacon, cheese, apple,smoke and fish flavorants, mint flavorants and combinations thereof. 7.A veterinary delivery system according to claim 1 wherein said film hasa moisture content of not greater than about 15% by weight.
 8. Aveterinary delivery system according to claim 1 wherein said film has amoisture content of about 3%-7% by weight.
 9. A veterinary deliverysystem according to claim 1 wherein said film has a moisture content ofabout 4-6% by weight.
 10. A veterinary delivery system according toclaim 1 wherein said film has a moisture content of about 4.5%-5.5% byweight.
 11. A veterinary delivery system according to claim 1 whereinsaid lubricant is selected from the group consisting of glycerins,glycols, oils and combinations thereof.
 12. A veterinary delivery systemaccording to claim 1 wherein said lubricant comprises propylene glycol.13. A veterinary delivery system according to claim 1 wherein saidlubricant comprises a fish oil.
 14. A veterinary delivery systemaccording to claim 1 wherein said lubricant comprises a vegetable oil.15. A veterinary delivery system according to claim 1 wherein saidbinder comprises polyvinyl alcohol.
 16. A veterinary delivery systemaccording to claim 1 wherein said binder comprises a methylcellulose.17. A veterinary delivery system according to claim 1 wherein saidbinder comprises hydroxypropyl methycellulose.
 18. A veterinary deliverysystem according to claim 1 wherein said film further comprises afiller.
 19. A veterinary delivery system according to claim 18 whereinsaid filler is selected from the group consisting of cornmeal,cornstarch, potato starch, bone meal, corn syrup, wheat germ, brewersyeast, xanthan gum, carrageenan and combinations thereof.
 20. Aveterinary delivery system according to claim 1 wherein said effective agent is selected from the group consisting of antibiotics, painrelievers, anti-inflammatory agents, antiviral agents, vaccines,wormers, heartwormers, nutritional supplements, hypothyroidismmedication, arthritis medication, agents for the control of tartar andplaque, incontinence medication, pain relievers, agents for treatment ofbacterial diseases and coccidiosis, nutritional supplements andcombinations thereof.
 21. A veterinary delivery system according toclaim 1 wherein said solvent comprises water.
 22. A veterinary deliverysystem according to claim 1 wherein said solvent comprises an organicsolvent.
 23. A veterinary delivery system according to claim 22 whereinsaid solvent comprises ethanol.
 24. A veterinary delivery systemaccording to claim 1 wherein said film further comprises at least onepreservative.
 25. A veterinary delivery system according to claim 24wherein said preservative is selected from the group consisting ofmethyl paraben, propylparaben, ethylenediamine-tetraacetic acid (EDTA),stearic acid, diazolidinyl urea, imdiazolidinyl urea, and combinationsthereof.
 26. A veterinary delivery system according to claim 1 whereinat least one pharmaceutically active component is soluble in saidsolvent.
 27. A veterinary delivery system according to claim 1 whereinat least one pharmaceutically active component is not soluble in saidsolvent.
 28. A veterinary delivery system according to claim 27 whereinsaid film has a moisture content of not greater than about 15% byweight.
 29. A veterinary delivery system according to claim 27 whereinsaid film has a moisture content of about 3%-7% by weight.
 30. Aveterinary delivery system according to claim 23 wherein said film has amoisture content of about 4%-6% by weight.
 31. A veterinary deliverysystem according to claim 23 wherein said film has a moisture content ofabout 4.5%-5.5% by weight.
 32. A veterinary delivery system according toclaim 1 wherein said effective agent is distributed homogeneouslythroughout said film.
 33. A veterinary delivery system according toclaim 1 wherein said effective agent is distributed on one side of saidfilm.
 34. A veterinary delivery system according to claim 33 whereinsaid effective agent is distributed homogeneously on one side of saidfilm.
 35. A veterinary delivery system according to claim 33 whereinsaid effective agent is distributed non-homogeneously on one side ofsaid film.
 36. A veterinary delivery system according to claim 1 whereinsaid effective agent is distributed non-homogeneously throughout saidfilm.
 37. A veterinary delivery system according to claim 1 wherein saideffective agent is disposed within micro-capsules distributed throughoutsaid film.
 38. A veterinary delivery system according to claim 1comprising a plurality of pharmaceutically active components.
 39. Aveterinary delivery system according to claim 1 comprising at least onepharmaceutically active agent and a cosmetic agent.
 40. A veterinarydelivery system according to claim 1 comprising at least one therapeuticagent and at least one cosmetic agent.
 41. A veterinary delivery systemaccording to claim 1 wherein said pliable film is hydrophilic.
 42. Aveterinary care delivery system comprising: a pliable film comprising:at least one binder; at least one lubricant; at least one solvent forsaid binder and said lubricant; an effective amount of at least oneeffective agent; and at least one flavorant.
 43. A veterinary caredelivery system according to claim 42 wherein said pliable film ishydrophilic.
 44. A veterinary care delivery system according to claim 42wherein said flavorant is selected from the group consisting of genuineand artificial beef, chicken, liver, bacon, cheese, apple, smoke, mintand fish flavorants and combinations.
 45. A veterinary care deliverysystem according to claim 42 wherein said film having a moisture contentof up to about 15% by weight.
 46. A veterinary care delivery systemaccording to claim 42 wherein said film has a moisture content of about3%-7% by weight.
 47. A veterinary care delivery system according toclaim 42 wherein said lubricant is selected from the group consisting ofglycerins, glycols, oils, and combinations thereof.
 48. A veterinarycare delivery system according to claim 42 wherein said lubricantcomprises propylene glycol.
 49. A veterinary care delivery systemaccording to claim 42 wherein said lubricant comprises a fish oil.
 50. Aveterinary care delivery system according to claim 42 wherein saidlubricant comprises a vegetable oil.
 51. A veterinary care deliverysystem according to claim 42 wherein said binder is selected from thegroup consisting of polyvinyl alcohol, methylcelluloses, gelatins,starches, and combinations thereof.
 52. A veterinary care deliverysystem according to claim 42 wherein said binder comprises hydroxypropylmethylcellulose.
 53. A veterinary care delivery system according toclaim 42 wherein said binder comprises a gelatin.
 54. A veterinary caredelivery system according to claim 42 wherein said binder comprises astarch.
 55. A veterinary care delivery system according to claim 42wherein said binder comprises polyvinyl alcohol.
 56. A veterinary caredelivery system according to claim 42 wherein said film furthercomprises a filler.
 57. A veterinary care delivery system according toclaim 56 wherein said filler is selected from the group consisting ofcornmeal, cornstarch, potato starch, bone meal, corn syrup, wheat germ,brewers yeast, xanthan gum, carrageenan and combinations thereof.
 58. Aveterinary care delivery system according to claim 42 wherein saideffective agent is selected from the group consisting of antibiotics,pain relievers, anti-inflammatory agents, anti-viral agents, vaccines,wormers, heartwormers, nutritional supplements, hypothyroidismmedication, arthritis medication, agents for the control of tartar andplaque, incontinence medication, pain relievers, agents for treatment ofbacterial diseases and coccidiosis, and combinations thereof.
 59. Aveterinary care delivery system according to claim 42 wherein saidsolvent comprises water.
 60. A veterinary care delivery system accordingto claim 42 wherein said solvent comprises an organic solvent.
 61. Aveterinary care delivery system according to claim 60 wherein saidsolvent comprises ethanol.
 62. A veterinary care delivery systemaccording to claim 42 wherein said film further comprises at least onepreservative.
 63. A veterinary care delivery system according to claim62 wherein said preservative is selected from the group consisting ofmethyl paraben, propylparaben, ethylenediaminetetraacetic acid (EDTA),stearic acid, diazolidinyl urea, imdiazolidinyl urea and combinationsthereof.
 64. A veterinary care delivery system according to claim 42wherein at least one effective agent is soluble in said solvent.
 65. Aveterinary care delivery system according to claim 42 wherein at leastone effective agent is not soluble in said solvent.
 66. A veterinarycare delivery system according to claim 42 wherein said effective agentis distributed homogeneously throughout said film.
 67. A veterinary caredelivery system according to claim 42 comprising a plurality ofeffective agents.
 68. A veterinary care delivery system according toclaim 42 comprising at least one pharmaceutically active agent and acosmetic agent.
 69. A veterinary delivery system according to claim 42comprising at least one therapeutic agent and at least one cosmeticagent.
 70. A method of delivering an effective agent to an animalcomprising the steps of: providing a pliable film comprising at leastone binder, at least one lubricant, at least one solvent for said binderand said lubricant, and an effective amount of at least one effectiveagent; and placing said film within the oral cavity of said animal. 71.A method of delivery an effective agent to an animal according to claim70 wherein said step of providing a pliable film comprises providing ahydrophilic film.
 72. A method of delivering an effective agent to ananimal according to claim 70 wherein said step of placing said filmwithin the oral cavity of an animal comprises placing said film on aninsert device and placing at least a portion of said insert devicewithin the oral cavity of said animal.
 73. A method of delivering aneffective agent to an animal according to claim 70 wherein said step ofplacing said film within the oral cavity of an animal comprises adheringsaid film to the tongue of said animal.
 74. A method of delivering aneffective agent to an animal according to claim 70 wherein said step ofplacing said film within the oral cavity of an animal comprises adheringsaid film to buccal membrane in said oral cavity of said animal.
 75. Amethod of delivering an effective agent to an animal according to claim70 wherein said step of providing a film comprises providing a filmcomprising a flavorant.
 76. A method of delivering an effective agent toan animal according to claim 70 wherein said step of providing a filmcomprises providing a film having a moisture content not greater thanabout 15% by weight.
 77. A method of delivering an effective agent to ananimal according to claim 70 wherein said step of providing a filmcomprises providing a film having a moisture content of about 3%-7% byweight.
 78. A method of delivering an effective agent to an animalaccording to claim 70 wherein said step of providing a film comprisesproviding a film having a moisture content of about 4%-6% by weight. 79.A method of delivering an effective agent to an animal according toclaim 70 wherein said step of providing a film comprises providing afilm having a moisture content of about 4.5%-5.5% by weight.
 80. Amethod of delivering an effective agent to an animal according to claim70 wherein said step of placing said film comprises the step of adheringthe film to the animal.